Effects of captopril on vascular reactivity of SHR in vivo and in vitro.
The effect of captopril treatment (100 mg/kg by mouth daily for up to 6 months) on pressor responses to norepinephrine (NE) and angiotensin II (AII) was examined in spontaneously hypertensive rats (SHR). Also, helical strips of rat aorta were removed from rats that had been similarly dosed. The aortic strips were suspended for isometric recording in modified Krebs' solution kept at 37 degrees C and bubbled with 95% O2-5% CO2. Pressor responses of both NE and AII in vivo were inhibited by captopril in SHR treated for all treatment periods. Responses to NE were more significantly and consistently inhibited than those for AII. Aortic strips from SHR previously dosed with captopril showed equivalent or greater contractile responses to potassium chloride (KCl) and NE, when compared with strips from untreated age-matched controls. In aortic strips from untreated Sprague-Dawley rats incubated with captopril, 30 micron g/ml for 1 hour ( a concentration 6000 times higher than that needed to inhibit angiotensin-covering enzyme by 50% in vitro), captopril had no effect on nitroglycerin-induced relaxation or NE-induced contractions, whereas ethacrynic acid (25 micron g/ml) reduced both the NE contractile response as well as the nitroglycerin-induced relaxation. These results suggest that captopril has no direct effect on the ability of isolated vascular smooth muscle to contract or relax despite causing a significant inhibition of pressor responses in vivo. It is suggested that this effect is related to an interaction of captopril with blood-borne elements necessary for the full expression of vasoconstriction, but unrelated to angiotensin-converting enzyme inhibition.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000627:therapeutic use*; D004976:Ethacrynic Acid / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats
D000804:Angiotensin II; D011189:Potassium Chloride; D011392:Proline; D002216:Captopril; D005996:Nitroglycerin; D004976:Ethacrynic Acid; D009638:Norepinephrine